Regulation of Caspase Activation

在动物身上，构成身体的细胞的行为必须在时间和空间上受到严格控制。这种控制在一定程度上源于一种内置的“自毁机制”，称为细胞凋亡。这一机制是在每个细胞内携带的，通过它，如果细胞变得潜在有害或不再需要，细胞就会被指示死亡。为了让动物保持健康，细胞凋亡必须受到严格的调控。事实上，许多人类疾病都是由于失去这一规定而导致的。例如，在癌症中，突变的细胞逃脱了凋亡，允许它们不适当地生长和分裂；结果是肿瘤。另一方面，当脑细胞发生不适当的凋亡时，就会导致神经退行性疾病。因此，维持细胞凋亡的正确平衡是至关重要的，但这一过程背后的分子机制还不是很清楚。因此，我们的目标是解开控制细胞凋亡的分子机制。我们的工作集中在一组被称为半胱氨酸天冬氨酸酶的高度专门化的酶上，它们是细胞凋亡程序的引擎。通过阐明caspase在正常条件下是如何被激活的，我们将更好地理解细胞凋亡在人类疾病中是如何被解除调控的。

In animals, the behaviour of the cells that make up the body must be tightly controlled in time and space. Part of this control stems from a built-in ?auto-destruct mechanism?, called apoptosis. This mechanism is carried within each cell, and through it the cell is instructed to die if it becomes potentially harmful or is no longer required. In order for an animal to remain healthy, apoptosis must be tightly regulated. Indeed, numerous human diseases result from the loss of this regulation. In cancer, for example, mutated cells escape apoptosis, allowing them grow and divide inappropriately; the consequence is a tumour. On the other hand, when brain cells undergo apoptosis inappropriately, neurodegenerative disease results. Thus maintenance of the correct balance of apoptosis is vital, but the molecular mechanisms underlying this process are not well understood. Our aim, therefore, is to unravel the molecular machinery that controls apoptosis. Our work concentrates on a group of highly specialised enzymes called caspases, which function as the engines of the apoptotic programme. By elucidating how caspases become activated under normal conditions, we will gain a better understanding of how apoptosis becomes deregulated in human diseases.